A 39-year-old woman, 14 months post–renal transplant and receiving tacrolimus, mycophenolate sodium, prednisolone, and trimethoprim/sulfamethoxazole prophylaxis, presented after 45 days of fever, hemoptysis, anorexia, and weight loss. Chest high-resolution computed tomography showed right upper-lobe consolidation with adjacent passive atelectasis and a left pleural effusion. Lung biopsy culture grew Aspergillus fumigatus, and a serum galactomannan optical density index of 8.16 met the 2020 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for invasive pulmonary aspergillosis.
Despite voriconazole and liposomal amphotericin B therapy, the patient developed altered sensorium and bilateral lower-limb weakness, prompting referral. Repeat transbronchial lung biopsy revealed suppurative inflammation and weakly acid-fast, branching, beaded filamentous organisms on Fite stain—morphology suggestive of Nocardia species. Physical exam had asymmetric upper motor neuron lower-limb weakness, neck stiffness, and coarse bilateral crackles on chest auscultation. Brain imaging demonstrated multiple ring-enhancing supratentorial lesions with central diffusion restriction and surrounding edema, consistent with disseminated central nervous system involvement.
Tissue culture on Sabouraud dextrose agar produced dry, chalky colonies consistent with Nocardia spp., but the study team could not achieve species-level identification. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) failed twice, and 16S rRNA sequencing was unavailable at the center. The authors reported antimicrobial susceptibility interpreted by disk diffusion on cation-adjusted Mueller–Hinton agar using Comité de l’Antibiogramme de la Société Française de Microbiologie thresholds. Results indicated resistance to trimethoprim/sulfamethoxazole and ciprofloxacin; the isolate appeared susceptible to linezolid, minocycline, imipenem, and amikacin.
The source noted that susceptibility testing for Nocardia is technically demanding, influenced by variable laboratory methods, lack of well-characterized control strains, and interlaboratory variability. The article did not provide species designation, minimum inhibitory concentration (MIC) values, or the raw disk-diffusion measurements.
The treating team diagnosed disseminated trimethoprim/sulfamethoxazole–resistant nocardiosis with pulmonary and cerebral involvement. They withheld tacrolimus and mycophenolate, continued low-dose prednisone, and initiated therapy with imipenem and linezolid while maintaining voriconazole for invasive aspergillosis. Clinical improvement was observed within one week of initiating therapy.
After one month, the patient developed cytopenias attributed to linezolid; linezolid was stopped and replaced with minocycline. Because of seizure risk, imipenem was switched to meropenem. The regimen ultimately consisted of meropenem plus minocycline, with meropenem continued for three months. Voriconazole treatment for aspergillosis was continued and stopped after six months. The article did not specify drug dosages, serum drug levels, or exact timing of each agent beyond the durations reported.
Follow-up imaging at six months documented resolution of both intracranial and pulmonary lesions, with residual pulmonary fibrosis on chest imaging and preservation of renal graft function. The patient remained clinically well at one-year follow-up and was maintained on secondary prophylaxis with minocycline. The source explicitly reported clinical and radiological resolution after six months and a favorable one-year outcome; no long-term graft surveillance metrics or functional neurologic outcome scales were provided.
The authors placed this case in context of variable reported resistance rates. They cited one U.S. study in which 42% of isolates appeared resistant to trimethoprim/sulfamethoxazole and 61% to sulfamethoxazole, while another multicenter comparison of 552 isolates across six reference labs reported only 2% resistance, attributing discrepancies to interlaboratory variability and challenges interpreting trailing MIC endpoints. Indian series were specifically referenced: a renal-transplant series with 16 nocardiosis cases found four resistant isolates among those receiving prophylaxis; a South India 10-year analysis reported 20.8% resistance among 48 cases; and a North India center reported 60% trimethoprim/sulfamethoxazole resistance among 12 renal transplant isolates, with 58.3% breakthrough infection while on prophylaxis. The article cautioned that reported prevalence varies with isolate source, geographic region, and susceptibility method.
The authors emphasized that brain imaging is indicated in all pulmonary nocardiosis cases regardless of neurologic symptoms because central nervous system involvement occurs in 20%–44% of cases. They also noted that species-level identification can be challenging: morphological and biochemical tests are often inconclusive, MALDI-TOF MS may be limited, and 16S sequencing may be unavailable in many centers.
Limitations reported in the source include the absence of species confirmation (MALDI-TOF failed twice and 16S sequencing was not performed) and lack of detailed susceptibility metrics such as MIC values. The report did not provide precise dosing regimens, therapeutic drug monitoring data, or explicit criteria used to attribute cytopenias to linezolid. Those unanswered operational questions remain relevant for centers managing similar cases and for establishing reproducible susceptibility workflows.